Compositions and methods for treating heart failure in diabetic patients

Abstract

The present invention provides the use of neuregulin protein for the preparation of medication for preventing, treating or delaying heart failure in humans and methods for preventing, treating or delaying heart failure in humans using said medication.

Description

[0001]This application is a U.S. national stage application of PCT / CN2012 / 001353, having an international filing date of Oct. 8, 2012, the entire contents of which are incorporated herein by reference.[0002]Incorporated herein by reference is the Sequence Listing being concurrently submitted via EFS-Web as an ASCII text file named 11748-048-999_Sequence_Listing.txt, created Mar. 19, 2015, and being 851 bytes in size.FIELD OF THE INVENTION[0003]The present invention relates to the use of neuregulin protein for the preparation of medication for preventing, treating or delaying heart failure in humans and methods for preventing, treating or delaying heart failure in humans using said medication. Particularly, the present invention provides methods for preventing, treating or delaying heart failure using the composition comprising a neuregulin protein in diabetic patients who has had or at high risk of a complication of heart diseases.BACKGROUND OF THE INVENTION[0004]Over recent years, ...

AI Technical Summary

Benefits of technology

[0015]In human clinical trials of neuregulin for treating heart failure, applicant discovered that heart failure patients who are diabetic patients will receive significant benefits from neuregulin treatment. Such benefits include significant reduction in mortality rate.

[0016]It has been discovered by applicant that NRG enhances cardiac muscle cell differentiation and organization of sarcomeric and cytoskeleton structure, as well as cell adhesion. It has been also discovered by applicant that NRG significantly improves or protects against deterioration in myocardial performance in distinct animal models of heart failure and in clinical trials. NRG is effective in improving myocardial structure, promoting survival of cardiomyocytes, promoting calcium homeostasis and its anti-atherosclerosis effect which are damaged in diabetic patients. Neuregulin, neuregulin polypeptide, neuregulin derivatives, or compounds which mimic the activities of neuregulins, fall within the scope of the present invention.

[0021]In a fifth aspect, the present invention provides a method to improve survival or reduce mortality of chronic heart failure patients, comprising administering a pharmaceutical composition comprising an effective amount of neuregulin to the chronic heart failure patients. In one embodiment, chronic heart failure patients are diabetic patients. In some embodiments, the pharmaceutical composition is administered to the patients intravenously or subcutaneously. In some embodiments, the pharmaceutical composition is administered to the patients for an introduction regimen. In some optimized embodiments, the introduction regimen includes continuous administration of the pharmaceutical composition for at least 3, 5, 7 or 10 days. In some better embodiments, the pharmaceutical composition is administered to the patients for a maintenance regimen for at least 6 months after the introduction. In some better embodiments, the maintenance regimen includes an administration of the pharmaceutical composition every 3, 5, 7 or 10 days.

[0042]As used herein, “survival” means the time or probability one subject may remain alive or living. It could be expressed by survival time or survival rate. Survival time is the time period start from the diagnosis or treatment to the end of the life. Survival rate means the percentage of people who are alive for a given period of time after diagnosis or treatment. For each subject, prolonged survival time caused by a treatment or interference could be regarded as a benefit. For a group of subjects or large populations, prolonged mean survival time or increased survival rate could be regarded as a benefit.

Problems solved by technology

DM is associated with a markedly increased risk of coronary artery disease which is the underlying cause of HF.

It may be resulted from impaired calcium handling in diabetic patients.

Otherwise, the renin-angiotensin system is unregulated with diabetes, and Angiotensin II (Mg II) locally may lead to oxidative damage, activating cardiac cell death.

Apoptosis and necrosis of myocytes may contribute to the development of a dilated myopathy which may result in heart failure.

Targeted disruption of the NRG-1β or ErbB2 or ErbB4 led to embryonic lethality due to cardiac development defects.

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